Understanding The Benefits Of Electrical Bone Stimulation

Approximately 6 million extremity fractures occur in the United States each year. Five to 10 percent of these fractures will go on to delayed or nonunion. In regard to lost wages and additional treatment for delayed and nonunions, this translates into an annual economic loss to the United States of $3 to $6 billion.

One of the vexing and controversial issues related to the use of electric bone stimulation regards the actual definition of when a delayed or a nonunion occurs. The historic definition of a nonunion by the FDA was that of osseous discontinuity of nine months’ duration in which there has been no evidence of osseous healing for three months. Fortunately, the general consensus today is that one can identify nonunion and delayed unions when there are no demonstrable or progressive signs of healing. This definition allows a much earlier and much more humane approach to the use of electronic bone stimulation.
 

A Guide To The Evolution Of Electrical Bone Stimulation

The discovery of the relationship between electricity and magnetism launched over 180 years of research into electrophysics and quantum mechanics. Today’s practical applications of this science include everything from the high speed mass storage hard drive to advanced imaging technologies and even a device that positively influences neo-osteogenesis. This device is better known as the electronic bone stimulator.

In the 1950s and 1960s, Fakada and Yasuda theorized that the bending of bone creates a strain that results in electrical streaming potentials within the bone. These studies correlated well with Wolff’s law whereby mechanical loads upon bone are translated into an electrical potential that contributes to the modeling of bone. Currently, the prevailing thinking is that these electrical potentials signal the body to begin the bone repair, modeling and remodeling processes. Application of these loads is known as mechanotransduction and this plays a crucial role in the physiology of many tissues including bone. Mechanical loading can inhibit bone resorption and increase bone formation in vivo.

What You Should Know About The Four Steps Of Mechanotransduction

In bone, the process of mechanotransduction can be divided into four distinct steps: mechanocoupling, biochemical coupling, transmission of signal and effector cell response. In mechanocoupling, mechanical loads in vivo cause deformations in bone that stretch bone cells within and lining the bone matrix and create fluid movement within the canaliculae of bone. Dynamic loading, which is associated with extracellular fluid flow and the creation of streaming potentials within bone, is most effective for stimulating new bone formation in vivo. Bone cells in vitro are stimulated to produce second messengers when exposed to fluid flow or mechanical stretch.

In biochemical coupling, the possible mechanisms for the coupling of cell-level mechanical signals into intracellular biochemical signals include force transduction through various complicated chemical pathways. The tight interaction of each of these pathways would suggest that the entire cell is a mechanosensor and there are many different pathways available for the transduction of a mechanical signal.

In the transmission of signal, osteoblasts, osteocytes and bone lining cells may act as sensors of mechanical signals and may communicate the signal through cell processes connected by gap junctions. These cells also produce paracrine factors that may signal osteoprogenitors to differentiate into osteoblasts and attach to the bone surface. Insulin-like growth factors and prostaglandins are possible candidates for intermediaries in signal transduction.

In the effector cell response, the effects of mechanical loading are dependent upon the magnitude, duration and rate of the applied load. Longer duration, lower amplitude loading has the same effect on bone formation as loads with short duration and high amplitude. Loading must be cyclic to stimulate new bone formation. Aging greatly reduces the osteogenic effects of mechanical loading in vivo. Also, some hormones may interact with local mechanical signals to change the sensitivity of the sensor or effector cells to mechanical load.

Understanding The Applications Of Bone Stimulation

Accordingly, the groundwork was established for the invention of electric bone stimulator devices. Modern investigators have given us a multitude of orthobiologic products to enhance native bone healing through the mechanisms of osteoinduction and enhanced osteogenesis. These products include platelet gels, demineralized bone matrix and bone morphogenic proteins. All of these products share a common mechanism. They all take advantage of growth factor proteins that form ligands with specific receptors on bone forming and bone inducing cell lines. Therein lies the elegance of the electric bone stimulation device. Researchers have shown that these devices create electromagnetic fields that mimic the same electric streaming potentials resulting from the bending of bone.

Furthermore, researchers have shown that the magnetic and electric fields created by these devices will act to increase the local production of insulin like growth factor II (IGFII), transforming growth factor beta (TGF-b) and specific bone morphogenic proteins (BMP) at the injury or osteotomy site. All of these compounds are required to heal bone.

How Do Electrical Stimulation Devices Fit Into The Bone Healing Armamentarium?

In general, bone healing will take place in a timely fashion when certain principles are in place. The principal ingredients to bone healing include proper nutrition, good vascularity, good stability across the fracture/fusion site, and the intrinsic properties of osteoinduction, osteogenesis and osteoconduction. Clearly, not all bone goes on to heal in a timely manner.

What available electric biophysical modalities tilt the scales in favor of bone healing as opposed to bony nonunion? In summary, they include direct current, capacitive coupling and pulsed electromagnetic field devices (PEMF).

Direct current bone stimulation is an invasive device. Physicians would place the implanted cathode portion of the device within the fracture/fusion site and place the battery-based anode in a remote subcutaneous position. A constant 20 –uA direct current transmits to the bone healing site. The prevailing thinking is that these devices decrease the local O2 tension, increase the local pH and increase local production of collagen and proteoglycans. There is no general consensus on when and if one needs to remove these devices when they are no longer required. I only remove those batteries that are in a subcutaneous position which leads to discomfort or might lead to an enhanced risk of soft tissue pressure induced breakdown, especially in the neuropathic patient. A significant advantage of this device is 100 percent patient compliance.

Pulsed electromagnetic field devices consist of magnetic coils that receive a pulsed electrical current. This results in a magnetic flux within the bone that is similar to endogenous electric streaming potential induced by bone strain. These devices work by increasing important cytokines like BMP and TGF-b. Clearly, the efficacy of this device relies upon the patient being very compliant regarding daily use. Fortunately, the LCD display allows the clinician the opportunity to monitor and track patient usage.

Capacitive coupling devices consist of two surface electrodes placed across from each other on the skin across a bone healing site. A 9-volt battery develops a sinusoidal wave signal across the bone. Researchers have shown this opens calcium channels and increases PGE-2, calmodulin and TGF-b. Compliance is also an issue with the capacitive coupling device, especially since it is recommended that the patient wears the device for greater than 20 hours per day. Fortunately, the battery pack is fairly compact and patients generally tolerate it well.

What The Research Reveals

Currently, there are over 700 peer-reviewed articles that elucidate the efficacy of this technology. In general, there is a reported range of healing efficacy between 50 and 85 percent with these devices. A full review of the literature is beyond the scope of this article but some evidence based, level-1 studies are noteworthy.

Mammi, et al., performed a randomized, double-blind prospective study looking at healing rates of high tibial osteotomies at 30 and 60 days. Patients were randomized to either a real or placebo PEMF device. The results showed a 72 percent healing rate in those with the active PEMF device and only a 26 percent healing rate at the 30- and 60-day marks with the placebo devices.1

Borsalino did a double-blind, prospective study looking at 31 femoral osteotomies, which were randomized to either a placebo or an active PEMF device. He found a 41 percent greater bone density and a 64 percent increased bone callus in the active group in comparison to the placebo group.2

Sharrard randomized 45 patients with tibial nonunions to either PEMF or placebo. After 12 weeks, 45 percent of the active PEMF units had solid union while only 14 percent of the placebo units had solid union within the same time frame of 12 weeks.3

In a very compelling laboratory study, Guerkov, et al., harvested tissue from eight patients with nonunions (four hypertrophic, four atrophic). The researchers isolated cells from these tissues and grew them to confluency. Study tissue underwent PEMF stimulation for eight hours a day while control tissue had no stimulation. The researchers harvested cells at one, two and four days. By day four, TGF-b levels were greater than 50 percent that of the controls via ELISA testing.4

A common thread for most research, both in vitro and in vivo, is that the efficacy of electric bone stimulation is time dependent with daily utilization being most effective between eight and 12 hours use per day for the PEMF devices.

Three Case Studies In Bone Stimulation

The following cases illustrate the valid use of electrical bone stimulation.

The first case involved a 63-year-old female who had a tibial-talar nonunion despite two previous attempts at treatment by another clinic. The patient subsequently developed a severe malposition secondary to progressive posterior tibial tendon dysfunction (PTTD). The correction entailed a tibial-calcaneal arthrodesis with intermetatarsal nail, external fixation and implantable direct current bone stimulation. She achieved good consolidation at just eight weeks postoperatively.

The second case involved a 49-year-old female with severe longstanding post-traumatic multilevel deformity. This patient had undergone 21 previous surgeries on her leg/foot for limb salvage over a 15-year period. In regard to her final reconstruction procedure, surgeons corrected the ankle deformity first and subsequently performed an open ankle arthrodesis. At 10 weeks after the attempted arthrodesis, she had obvious delayed union. The final radiograph shows good union at eight weeks after we applied a PEMF device.

The third case involves a 60-year-old patient with rheumatoid arthritis and a tibial varum deformity. The center of rotation of angulation (CORA) was midshaft. Accordingly, this was a high risk bone healing site. The patient underwent corrective tibial osteotomy and a tibio-talar-calcaneal arthrodesis.

After we performed a proximal tibial osteotomy, we had the patient wear a capacitive coupling bone stimulation device 24 hours a day for 12 weeks. We utilized a direct current implantable device at the distal ankle. The patient achieved good union at 16 weeks postoperatively.

In Conclusion

In summary, electrical bone stimulation is an effective orthobiologic adjunct to the healing of high risk fusion/fractures and of confirmed biologically active non- and delayed unions. Clearly, physicians must use good judgment when utilizing these modalities due to economic concerns.

I reserve use of this technology for patients who are undergoing arthrodesis/ osteotomies and have comorbidities that may act to inhibit normal bone healing. I will also use this modality for those patients who lack the obvious progression of bone healing one would expect with normally timed serial radiographs. In general, physicians may consider these devices on a case by case basis.

Electric bone stimulation seems to be a very adaptable and efficacious adjunctive treatment. Exciting future applications may possibly include soft tissue healing indications, fresh fracture healing, cartilage regeneration and even external fixation devices that include electromagnetic skinny wires and half pins.

References:

1. Mammi, et al. Effect of PEMF on the healing of high tibial osteotomies: a double blind study. Clin Orthop Relat Res 288: 246-253, 1993.
2. Borsalino, et al. Electrical stimulation of human femoral intertrochanteric osteotomies:double blind study. Clin Orthop Relat Res 237:256-63, 1988.
3. Sharrard, et al. A double blind trial of pulsed electromagnetic fields for delayed union of tibial fractures. J Bone Joint Surg Br, 72 (3): 347-55, 1990.
4. Guerkov HH, et al. Pulsed electromagnetic fields increase growth factor release by nonunion cells. Clin Orthop Relat Res. 384:265, 2001.
5. Duncan, et al. Mechanicotransduction and the functional response of bone to mechanical strain. Calcif Tissue Int. 57(5):344-58, 1995.